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Citi says Ionis Pharmaceuticals has blasted a "home run" with its data for Tryngolza as a treatment for severe hypertriglyceridemia. Ionis Pharmaceuticals has hit a “home run,” according to analysts at Citi, with data in two phase 3 trials that show the ability of Tryngolza (olezarsen) to reduce triglycerides and acute pancreatitis (AP) events in individuals with severe hypertriglyceridemia (sHTG).In the largest sHTG study ever run, the trials achieved their primary endpoint with placebo-adjusted reductions of 55% and 72% in triglycerides after six months of treatment. Pooled data from the trials also showed as a secondary prespecified endpoint that Tryngolza reduced the risk of AP events by 85% after patients were on Tryngolza for a year.“Taken together, we view these data as the best-case scenario for Ionis and substantially exceeding our expectations,” Myles Minter, Ph.D., of William Blair wrote.Meanwhile, analysts from Jefferies jacked up their peak sales potential of Tryngolza from $1.5 billion to $2.5 billion.Ionis said that it will present full results at a future medical meeting and plans to submit for FDA approval of Tryngolza in sHTG by the end of this year and to regulators outside of the U.S. in 2026.With the results, Ionis’ share price zoomed by 33% by publication time on Tuesday morning.“We believe that this is an unprecedented and historical achievement in the field of lipidology, where the quest to reduce the risk of acute pancreatitis in sHTG has been ongoing for nearly 50 years,” Sam Tsimikas, M.D., Ionis’ chief of global cardiovascular development, said during a Tuesday webcast.The CORE and CORE2 studies included 1,063 sHTG patients who were required to be on standard-of-care lipid-lowering therapy throughout. In both trials, Tryngolza was tested at 80mg and 50mg doses, each injected monthly. In CORE, which included 617 patients, the placebo-adjusted triglyceride reductions were 72% and 63% at the respective doses. In CORE2, which included 446 participants, the placebo-adjusted triglyceride figures came in at 55% and 49% at the respective doses.Helping explain the differences in the trials was that at baseline, 47% and 37% of participants had fasting triglycerides of at least 880 mg/dL in CORE and CORE2, respectively. Levels below 150 mg/dL are typically considered healthy for adults. In CORE, the placebo group had a 0.5% reduction in triglycerides, compared to a 14% reduction in triglycerides in the placebo group in CORE2.“Olezarsen had a very large treatment effect, reducing the risk of pancreatitis by 85% in only one year of treatment, definitely proves the link between elevated triglycerides and acute pancreatitis in sHGT,” Tsimikas added. Self-injected Tryngolza is an RNA-targeted ligand conjugated antisense (LICA) medicine designed to lower the body's production of apolipoprotein C-III (apoC-III) in the liver. The FDA approved the drug in December of last year as the first drug to treat familial chylomicronemia syndrome (FCS), a disorder that prevents the body from breaking down fats, leading to elevated triglyceride levels in the blood. The underdiagnosed condition affects an estimated 3,000 people in the U.S.By contrast, a much larger patient population awaits in sHTG, which affects approximately 3 million in the U.S., including roughly 1.2 million who are considered high-risk. Those in the high-risk group have triglyceride counts of greater than 880 mg/dL or greater than 500 mg/dL for those who have a history of AP.“At launch, we plan to prioritize high-risk sHTG treaters in the U.S. made up of cardiologists, endocrinologists and lipidologists. These specialists manage the vast majority of the high-risk sHTG patient population,” Kyle Jenne, Ionis’ commercialization chief, said on Tuesday. “We expect the drug will be very well-received by physicians and payors alike, as both have strong interest in avoiding expensive and potentially deadly pancreatitis hospitalizations for sHTG patients,” Citi analysts David Lebowitz and Ike Lee wrote. “Additionally, we believe premium pricing could be justified for Tryngolza as the sole therapy to have shown such benefits on reducing pancreatitis.”The sHTG results come less than two weeks after Ionis secured an FDA approval for Dawnzera to treat a rare genetic condition, hereditary angioedema (HAE).

Dive Brief:Ionis on Tuesday said its new lipid-lowering drug Tryngolza met the main goals of two Phase 3 clinical trials that could expand its use. Results showed the drug significantly reduced triglyceride levels in people with severely elevated levels of the fat in their bloods and prevented accompanying pancreatitis episodes.The company will ask the Food and Drug Administration by the end of the year to add severe hypertriglyceridemia to Tryngolzas label. The drug, Ionis first wholly owned product, gained approval in December for a rare inherited condition called familial chylomicronemia syndrome, for which it recorded $25.6 million in sales over the first six months of 2025.Ionis shares rose as much as 34% in morning trading. Leerink Partners analyst Mani Foroohar wrote in a note to clients that the data easily meet our blue-sky scenario for the drug because it gives Tryngolza a bolstered position in a multi-billion dollar market.Dive Insight:Ionis specializes in drugs that block RNA responsible for production of proteins implicated in certain genetically driven diseases. For example, its drug Spinraza, which Biogen sells, treats spinal muscular atrophy, which can be a fatal condition for many babies and children.Until the launch of Tryngolza, Ionis strategy was to license drugs to larger partners like Biogen and AstraZeneca, which have larger commercial arms to reach more physicians and patients. Since Tryngolza, Ionis has also launched a second wholly owned drug called Dawnzera for hereditary angioedema.Tryngolza, which Ionis launched with a list price of $595,000 a year, is approved for a rare condition that affects as many as one in 300,000 people. The potential addition of people with severely elevated triglycerides a condition that is growing with prevalence of obesity and diabetes represents a large expansion opportunity for Tryngolzas market.Called Core and Core2, Ionis trials enrolled 617 and 446 people with severely elevated triglycerides and randomized them to take 80 milligrams or 50 milligrams of Tryngolza every four weeks, or placebo. In Core, the 80 or 50 milligram doses of the drug reduced triglycerides by 73% and 63% respectively, and in Core2 the reductions were 68% and 63%, respectively.In Core, people who received placebo experienced triglyceride lowering of less than 1% on average, while in Core2 it was 14%. The reductions seen in people taking Tryngolza were statistically significant compared with the placebo.Treatment with Tryngolza reduced the incidence of acute pancreatitis by 85% compared with placebo, but Ionis didnt release results from the individual dose arms.These results reinforce our confidence that olezarsen has the potential to change the [severe hypertriglyceridemia] treatment paradigm, said Sam Tsimikas, Ionis senior vice president for global cardiovascular development, in a statement.Jefferies analyst Akash Tewari raised his banks peak sales forecast for Tryngolza from $1.5 billion to $2.5 billion, with the elevated triglyceride indication in the U.S. accounting for about $1.5 billion of the total. '